The overall goal of this project is to better understand the role in cellular regulation of efflux of cyclic AMP from the cell, and in particular the role of efflux of cyclic AMP into the urine in the hormonal regulation of the kidney. To date it has been shown that the organic anion transport inhibitor probenecid blocks the efflux of cyclic AMP into the urine in response to parathyroid hormone (nephrogenous cyclic AMP), and also the efflux of cyclic AMP from cultured kidney epithelial cells, suggesting that efflux is a carrier-mediated process. The efflux system for cyclic AMP in kidney cells (LLC-PK1) is insensitive to inhibition by prostaglandin A1 and relatively insensitive to cold, and thus different from that present in cultured fibroblasts and in erythrocytes. Its inhibition results in increased accumulation of intracellular cyclic AMP. Goals for the coming year include determination of the role of efflux as a modulator of hormone action in vivo: does inhibition of the efflux of cyclic AMP from tubular cells potentiate the phsophaturic and other effects of parathyroid hormone? The efflux carrier in cultured cells will be further characterized by photoaffinity labelling.